title: Kinetics of phenylalanine transport at the human blood-brain barrier investigated in vivo.
abstract: In vivo proton magnetic resonance spectroscopy was used to investigate intracerebral phenylalanine (Phe) concentrations in nine patients with classical phenylketonuria (PKU). The study included serial examinations (n = 31; plasma Phe levels: 0.47-2.24 mmol/l) of patients either receiving a Phe-restricted diet (200 mg Phe per day; four patients) or a diet rich in Phe (1000 mg Phe per day; three patients). No spectrum showed metabolic abnormalities besides elevated Phe. Difference spectroscopy yielded intracerebral Phe concentrations between 0.20 and 0.76 mmol/l. Regional variations between parieto-occipital periventricular brain, frontal brain, and cerebellum were not statistically significant. Data could be fitted assuming saturable Phe transport into the brain, based on a symmetric Michaelis-Menten model (characterized by an apparent Michaelis transport constant, K(t,app), and a maximum transport velocity, Tmax) and constant Phe consumption in the brain cells (described by a velocity Vmax). Non-linear least-squares fitting of the combined data from all patients yielded K(t,app) = 0.16 +/- 0.11 mmol/l and (Tmax / Vmax) = 9.0 +/- 4.1. Carrier saturation and competitive inhibition of the influx of other large neutral amino acids can be expected at plasma Phe levels usually found in PKU patients.
authors.affiliation: Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC 27710, USA. hem@orion.mc.duke.edu
authors.forename: H E
authors.initials: HE
authors.lastname: Möller
authors.forename: J
authors.initials: J
authors.lastname: Weglage
authors.forename: D
authors.initials: D
authors.lastname: Wiedermann
authors.forename: P
authors.initials: P
authors.lastname: Vermathen
authors.forename: U
authors.initials: U
authors.lastname: Bick
authors.forename: K
authors.initials: K
authors.lastname: Ullrich
mesh_terms: D000293:Adolescent; D000328:Adult; D001812:Blood-Brain Barrier / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology; D002648:Child; D005260:Female; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010649:Phenylalanine / Q000493:pharmacokinetics*; D010661:Phenylketonurias / Q000378:metabolism*
chemical_list: D010649:Phenylalanine